Carotenoids and retinoids are naturally occurring substances which contain extensively conjugated polyene chains. Carotenoids have the most extensively conjugated systems of carbon-carbon double bonds which give rise to their many varied and brilliant colors. Many carotenoids and retinoids, which are naturally occurring substances, are biologically active. For example, certain hydrocarbon members of the carotenoid family (most notably, .beta.-carotene, or pro-vitamin A, one of the most abundant carotenoids in food) are sources of retinol (one form of vitamin A); carotenoids protect plants from photosensitized oxidative damage, probably by deactivating singlet oxygen; epidemiological evidence indicates that carotenoid intake correlates inversely with the incidence of some types of cancer (Peto et al, Nature, 1981, 290, 201-208). Carotenoids and retinoids have been shown to retard the development of some experimentally induced animal tumors (N. I. Krinsky. Actions of Carotenoids in Biological Systems, Annu. Rev. Nutr, 13, 561-587 (1993); Matthews-Roth, Curr. Top. Nutr. Dis. [New Prot. Roles Select. Nutr.], 1989, 22, 17-38; Pure Appl. Chem., 1985, 57, 717- 722); a number of dietary intervention studies are being carried out to try to determine the efficacy of supplemental .beta.-carotene as a non-toxic, dietary anti carcinogen that can effectively decrease cancer mortality and most recently the possibility has begun to be examined that .beta.-carotene may be associated with decreased incidence of coronary heart disease; recent clinical data with the use of related compounds (retinoids--retinoic acid, retinol and retinamides) have demonstrated a role in anti-cancer therapy, both as a therapeutic and a preventive agent (cancers of the skin, head and neck, lung and bladder, acute promyelocytic leukemia, leukoplakia and myelodysplastic syndromes; D. L. Hill and C. J. Grubs, Retinoids and Cancer Prevention, Annu. Rev. Nutr. 1992, 12, 161-181); and finally, .beta.-carotene has antioxidant properties at the low oxygen pressures found in tissues (Burton and Ingold, .beta.-Carotene: an unusual type of lipid antioxidant, Science, 1984, 224, 569-573).
Carotenoids, retinoids and related conjugated polyenes are reactive towards molecular oxygen (O.sub.2) and may therefore be oxidatively degraded in foodstuffs during storage, even at reduced temperatures. Carotenoids are more reactive than retinoids towards oxygen because of their larger, more extensively conjugated system of double bonds. The products of such oxidative degradation of carotenoids retinoids, and related conjugated polyenes and their potential physiological activities have, nevertheless, received remarkably little attention, with the exception of vitamin A, which is obtained as a product of the biological oxidation of .beta.-carotene.
Mordi et al, Exploratory study of .beta.-carotene Autoxidation, published in Tetrahedron Letters, 1991, 32 (33), 4203-4206, examined the products formed during the self-initiated autoxidation of .beta.-carotene. The paper concludes that the main products identified in the early stages of .beta.-carotene autoxidation are epoxides, .beta.-ionone, .beta.-apo-13-carotenone, retinal, and related carbonyl compounds; in the final mixture, short chain carbonyl compounds predominate.
Another paper by Mordi et al, "Oxidative Degradation of .beta.-carotene and .beta.-Apo-8'-carotenal", published in Tetrahedron Vol. 49, No. 4, pp. 911-928, Jan. 22, 1993, shows that self-initiated oxidation of .beta.-carotene with molecular oxygen produces epoxides, dihydrofurans, carbonyl compounds, carbon dioxide, traces of alcohols, and some other compounds. The paper, co-authored by one of the present inventors, also makes a mention of some polymeric/oligomeric material which frequently deposited out of solution, particularly in the later stages of .beta.-carotene oxidation. The properties of the polymer/oligomer are not disclosed in the paper.
This patent application results from the development of our idea that the biological activity of carotenoids derives not from the carotenoids themselves but instead from one or more of their oxidation products generated in vivo. Retinoids are also included because of their ability to oxidize, although not as readily as carotenoids. The biological activity of oxidized retinoids is distinct from the known activity of the retinoids themselves.